Elevated serum soluble endoglin (sCD105) decreased during extracorporeal elimination therapy for familial hypercholesterolemia
ABSTRACT Extracorporeal elimination is a method of LDL-lowering therapy that is used in severe familial hypercholesterolemia (FH) after other therapeutic approaches have failed. There are currently no universally accepted biomarkers that would allow determining necessary intensity of therapy and frequency of future therapeutic interventions. An ideal tool for immediate evaluation would be a readily measurable serum marker. We hypothesized that soluble endoglin (sCD105), a recently described indicator of endothelial dysfunction, may represent such a tool. Eleven patients with FH (three homozygous, eight heterozygous; Fredrickson type IIa, IIb) that have been monitored for 4.5+/-2.8 years were treated; eight by LDL-apheresis and three by hemorheopheresis. 40 sCD105 measurements were done, before and after two consecutive elimination procedures. Baseline serum sCD105 levels were significantly higher in the patients (5.74+/-1.47 microg/l in series I, 6.85+/-1.85 microg/l in series II) than in the control group (3.85+/-1.25 microg/l). They decreased to normal after LDL-elimination (p=0.0003) in all except for one patient. This return to normal was not due to a non-specific capture of endoglin in adsorption or filtration columns as demonstrated by measurement of sCD105 before and after passage through the elimination media. We conclude that the soluble endoglin levels in patients with severe FH remain elevated despite long-term intensive therapy and that they decrease after extracorporeal elimination. Endoglin can therefore serve as a marker for evaluation of the treatment efficacy and of the decreased atherosclerotic activity in patients with FH treated by extracorporeal LDL-cholesterol elimination.
- SourceAvailable from: Pavel Rozsival
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- "During our long-term research of AMD and other microcirculation disorders, we have studied markers of clinical activity and the possibilities of improving the clinical state after extracorporeal elimination. We have found changes in markers of apoptosis, several cytokines, interleukins, or endoglin . Obtaining these markers is technically difficult and relatively expensive, and the results are not immediately available. "
ABSTRACT: Background: Rheohemapheresis (RHF) is a method that can stop the activity of the dry form of age-related macular degeneration (AMD). The pathophysiologic mechanisms are not well understood, and the effects of the RHF procedures extend beyond the time of the individual procedures. Patients and methods: We present the data for 46 patients with AMD treated with a series of 8 rheohemapheretic procedures. Blood count parameters were measured before the first and the last procedures. The clinical effect was judged by changes in the drusenoid pigment epithelium detachment (DPED) area before and after the rheopheretic sessions. Results: Rheopheresis caused a decrease in hemoglobin (P<0.001), a decrease in leukocytes (P<0.034), and an increase in platelets (P<0.005). We found a negative correlation between the amount of platelets and their volume (P<0.001, Pearson correlation coefficient: -0.509). We identified the platelet/MPV ratio as a good predictor of the clinical outcome. Patients with a platelet/MPV ratio greater than 21.5 (before the last rheopheresis) had a significantly better outcome (P=0.003, sensitivity of 76.9% and specificity of 80%). Conclusion: Several basic blood count parameters after RHF can be concluded to significantly change, with some of those changes correlating with the clinical results (reduction of the DPED area).01/2013; 2013:858219. DOI:10.1155/2014/858219
Atherogenesis, 01/2012; , ISBN: 978-953-307-992-9
- "Endoglin colocalization with eNOS in aortic endothelial cells in mice atherosclerosis was also demonstrated (Nachtigal et al., 2009b). More recently, it was demonstrated that endoglin serum levels are decreased by extracorporeal LDL-cholesterol elimination in patients with familial hypercholesterolemia, suggesting that endoglin can serve as a marker for evaluation of the treatment efficacy of these procedure (Blaha et al., 2008). "
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ABSTRACT: Increased levels of a soluble form of endoglin (sEng) circulating in plasma have been detected in various pathological conditions related to cardiovascular system. High concentration of sEng was also proposed to contribute to the development of endothelial dysfunction, but there is no direct evidence to support this hypothesis. Therefore, in the present work we analyzed whether high sEng levels induce endothelial dysfunction in aorta by using transgenic mice with high expression of human sEng. Transgenic mice with high expression of human sEng on CBAxC57Bl/6J background (Sol-Eng+) and age-matched transgenic littermates that do not develop high levels of human soluble endoglin (control animals in this study) on chow diet were used. As expected, male and female Sol-Eng+ transgenic mice showed higher levels of plasma concentrations of human sEng as well as increased blood arterial pressure, as compared to control animals. Functional analysis either in vivo or ex vivo in isolated aorta demonstrated that the endothelium-dependent vascular function was similar in Sol-Eng+ and control mice. In addition, Western blot analysis showed no differences between Sol-Eng+ and control mice in the protein expression levels of endoglin, endothelial NO-synthase (eNOS) and pro-inflammatory ICAM-1 and VCAM-1 from aorta. Our results demonstrate that high levels of soluble endoglin alone do not induce endothelial dysfunction in Sol-Eng+ mice. However, these data do not rule out the possibility that soluble endoglin might contribute to alteration of endothelial function in combination with other risk factors related to cardiovascular disorders.PLoS ONE 03/2015; 10(3):e0119665. DOI:10.1371/journal.pone.0119665 · 3.23 Impact Factor